Trouble spots. In mice infected with the H5N1 virus, deposits of phosphorylated alpha-synuclein (arrows) in dopamine neurons may be a sign of neurodegeneration.
Credit: H. Jang et al., PNAS Early Edition (2009)
Posted on 08/13/2009 12:56:27 AM PDT by neverdem
Trouble spots. In mice infected with the H5N1 virus, deposits of phosphorylated alpha-synuclein (arrows) in dopamine neurons may be a sign of neurodegeneration.
Credit: H. Jang et al., PNAS Early Edition (2009)
Decades after the 1918 influenza pandemic, epidemiologists noted an uptick in the number of people with diminished mobility and other neurological symptoms reminiscent of Parkinson's disease. But despite this and other hints, the idea that viruses can trigger neurodegenerative disease has remained controversial. Now researchers report new evidence for such a link: Mice infected with the H5N1 avian influenza virus lose the same dopamine-releasing neurons that are destroyed by Parkinson's disease.
The new study was inspired in part by video footage of chickens, geese, and ducks collected in Laos by researchers working with the World Health Organization's surveillance program, says senior author Richard Smeyne, a developmental neurobiologist at St. Jude Children's Research Hospital in Memphis, Tennessee. "The birds looked like they had Parkinson's disease," Smeyne says. "They were tremoring, falling side to side, and having difficulty with movements." So far there have been no reports of Parkinson's disease in human survivors of the H5N1 flu, Smeyne says, but because only a few years have passed since the first cases were reported, it's too early to know whether those infected are at increased risk.
To learn more about the virus's effect on the nervous system, Smeyne and colleagues sprayed a solution containing the virus into the noses of 225 mice. All of the mice developed tremors and movement difficulties. Using an antibody that binds and labels a specific viral protein, the researchers tracked the virus as it first infected nerves in the gut 2 or 3 days after the nasal spray and then successively appeared in the brain stem and midbrain and ultimately infected much of the rest of the brain within 10 days. By 21 days, mice had cleared the virus. But at the end of the 90-day study, the brain regions that had been infected still exhibited signs of inflammation and had elevated levels of phosphorylated alpha-synuclein, the main ingredient in the abnormal clumps of protein that are a hallmark of Parkinson's and certain other neurodegenerative diseases, the researchers report online this week in the Proceedings of the National Academy of Sciences. The researchers also report that the number of dopamine-releasing neurons in the substantia nigra--the neurons that die off in Parkinson's disease--declined by 17% in the infected mice.
Smeyne notes that 17% is a small reduction compared with the 70% or so loss of dopamine neurons in people with full-blown Parkinson's disease. He suspects that H5N1 infection alone is insufficient to cause Parkinson's, but it may make the brain more susceptible, especially in combination with other factors, such as unlucky genetics, another environmental trigger, or simply old age.
"It's a very exciting paper," says Malú Tansey, a neuroscientist who studies inflammation and neurodegenerative disease at Emory University in Atlanta. Tansey says Smeyne's team has provided compelling evidence that the virus can sneak into the brain via the peripheral nervous system and that it plays a role in killing dopamine neurons. That said, she doesn't see the findings as cause for panic. "I don't think people should be overly concerned if they're exposed to avian flu virus that they're going to get Parkinson's disease," Tansey says. "But it should prompt [more] investigators to reexamine inflammation as a potential contributing factor to neurodegenerative disease."
Highly pathogenic H5N1 influenza virus can enter the central nervous system and induce neuroinflammation and neurodegeneration
Haeman Janga, David Boltzc, Katharine Sturm-Ramirezc, Kennie R. Shepherda, Yun Jiaoa, Robert Webster and Richard J. Smeyne
Abstract
One of the greatest influenza pandemic threats at this time is posed by the highly pathogenic H5N1 avian influenza viruses. To date, 61% of the 433 known human cases of H5N1 infection have proved fatal. Animals infected by H5N1 viruses have demonstrated acute neurological signs ranging from mild encephalitis to motor disturbances to coma. However, no studies have examined the longer-term neurologic consequences of H5N1 infection among surviving hosts. Using the C57BL/6J mouse, a mouse strain that can be infected by the A/Vietnam/1203/04 H5N1 virus without adaptation, we show that this virus travels from the peripheral nervous system into the CNS to higher levels of the neuroaxis. In regions infected by H5N1 virus, we observe activation of microglia and alpha-synuclein phosphorylation and aggregation that persists long after resolution of the infection. We also observe a significant loss of dopaminergic neurons in the substantia nigra pars compacta 60 days after infection. Our results suggest that a pandemic H5N1 pathogen, or other neurotropic influenza virus, could initiate CNS disorders of protein aggregation including Parkinson’s and Alzheimer’s diseases.
Hat tip to Dvdmom who sent the abstract to me before I had a reason to look at ScienceNOW Daily News.
Darn! I forget where I read the article, it was so long ago, but yes, either it was the 1918 virus or a different one that came along in the 1920’s.
People survived it but gradually were afflicted with Parkinson’s-like symptoms some years later. These were the “Awakenings” people that Dr. Oliver Sacks cut his teeth on in the 1960’s.
However, I don’t know what proportion of survivors contracted the parkinsonian symptoms or how many of them became the extreme, frozen people of the book/movie.
The newly discovered L-dopa wrought miracles but gradually lost it’s effectiveness and brought on nasty side-effects and eventually they were all frozen again.
Or something like that...
Ping...(Thanks, neverdem!)
Appreciate the Bird Flu ping. Do you know if anyone is keeping a Parkinson’s ping list? I would like to be added if there is one.
SWINE FLU VICTIM'S FAMILY PLAN TO SUE NYC FOR $40 MILLION
A Common Heartburn Remedy Complements Conventional Cancer Therapy my thread
Cimetidine: A Common Heartburn Remedy Complements Conventional Cancer Therapy Hat tip to oprahstheantichrist, her thread, & Rockingham, his warnring about zinc deficiency!
FReepmail me if you want on or off my health and science ping list.
I don't believe there is one. Someone could volunteer to start one.
I would like to be added if there is one.
So would I. I have a bunch of lists already. I would be happy to link it on my health & science threads. I already link my microbiology, stem cell and diabetes lists to them.
You might do a keyword search for Parkinson's, too.
Ping :))
Smokin’ Joe you are a charter member.
Neverdem, please link to your health and science threads. Do you want on the ping list? Please add me to the diabetes ping list.
Anyone else on the Parkinson's Ping List? My interest is early onset PD — my 23 year old son has a classic case of PD 40 years ahead of schedule.
This is one. See comment# 5 with the links. Here's another: Aspirin improves survival after colorectal cancer diagnosis
Do you want on the ping list?
Add me to your Parkinson's disease list, please.
Please add me to the diabetes ping list.
Done already.
Thank you
If you’re starting a ping list, please add me.
After 10 years, the neurologist told me last week that he is changing my mother’s diagnosis from Parkinson’s to Progressive Supranuclear Palsy. Are you familiar with this?
Sorry to hear about your son.
My best regards
Not very. I read this pfd link that eventually came from your link. I read about two thirds of it until they mentioned making brain donations after the time came. If you haven't read it, you should. I think you'll agree or disagree with the change in diagnosis. Maybe some of your mom's meds can be discontinued if there are side effechts causing problems.
http://www.psp.org/doc_library/1217970611/Some%20Answers.pdf
Not very. I read this pfd link that eventually came from your link. I read about two thirds of it until they mentioned making brain donations after the time came. If you haven't read it, you should. I think you'll agree or disagree with the change in diagnosis. Maybe some of your mom's meds can be discontinued if there are side effechts causing problems.
http://www.psp.org/doc_library/1217970611/Some%20Answers.pdf
Thank you, Owen!
I think it has to be pretty much mega doses, 1200mg/day for it to really work, but many have had great results.
Best regards,
OTAC
I had previously run across another article about CoQ10. Thanks for the link!
You are added to the list. Please ping me to anything you run across.
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